Mitogen-activated protein kinase p38-2 and methods of use therefor

Abstract

Compositions and methods are provided for the treatment of diseases associated with mitogen activated protein kinase cascades. In particular, the mitogen-activated protein kinase p38-2, and polypeptide variants thereof that stimulate phosphorylation and activation of substrates such as ATF2, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the p38-2 kinase cascade. Such polypeptides and agents may also be used for the treatment of diseases associated with mitogen-activated protein kinase cascades.

1. A method for identifying a composition that modulates signal transduction via a MAP kinase cascade, comprising:
 a) incubating components comprising the composition, a p38-2 polypeptide, and a p38-2 substrate, under conditions sufficient to allow the components to interact, wherein said p38-2 polypeptide is encoded by a polynucleotide that comprises the nucleotide sequence of SEQ ID NO:1; and 
 b) measuring the effect of the composition on the phosphorylated state of the substrate; and 
 c) comparing the level of phosphorylation of the substrate with that achieved using a p38-2 polypeptide without incubation with the composition. 
 
     
     
       2. A method for identifying a composition that modulates signal transduction via a MAP kinase cascade, comprising:
 a) incubating components comprising the composition, a p38-2 polypeptide, and a p38-2 substrate, under conditions sufficient to allow the components to interact, wherein said p38-2 polypeptide is encoded by a polynucleotide that comprises the nucleotide sequence of SEQ ID NO:1; and 
 b) measuring the effect of the composition on p38-2 kinase activity; and 
 c) comparing the level of p38-2 kinase activity with that achieved using a p38-2 polypeptide without incubation with the composition. 
 
     
     
       3. A method for identifying a composition that modulates signal transduction via a MAP kinase cascade, comprising:
 a) inserting a polynucleotide encoding a p38-2 polypeptide into an expression vector, wherein said polynucleotide comprises the nucleotide sequence of SEQ ID NO:1; 
 b) expressing the polynucleotide encoding the p38-2 polypeptide; 
 c) incubating components comprising the composition, the expressed p38-2 polypeptide of step b), and a p38-2 substrate, under conditions sufficient to allow the components to interact: 
 d) measuring the effect of the composition on the phosphorylated state of the substrate; and 
 e) comparing the level of phosphorylation of the substrate with that achieved using the expressed p38-2 polypeptide of step b) without incubation with the composition. 
 
     
     
       4. The method of  claim 1 ,  2  or  3 , wherein said composition modulates signal transduction via the p38-2 kinase cascade. 
     
     
       5. The method of  claim 1 ,  2  or  3 , wherein the p38-2 polypeptide comprises the sequence of SEQ ID NO:2. 
     
     
       6. The method of  claim 1 ,  2 , or  3  wherein the p38-2 substrate is selected from the group consisting of ATF2, MAPKAP kinase 2 and MAPKAP kinase 3.